Sandbox Reserved 1095: Difference between revisions

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=== Primary and secondary structure ===

AT1 receptor consists in a 376 amino acid string <ref> [http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?pdbcode=4zud&template=main.html Protein Database (PDBsum): 4zud. European Bioinformatics (EBI); 2013.]</ref>. The protein is composed of

<scene name='82/829348/Helix_a/1'>18 ~~alpha~~ helix</scene>

<scene name='82/829348/Helix_a/1'>18 α helix</scene>

and <scene name='82/829348/B_sheet/1'>3 β sheets</scene>. Moreover, 7 ~~alpha~~ helix are made of a majority of hydrophobic amino acids. These helix are long enough to cross the membrane and create an <scene name='82/829348/Transmambrane_protein/1'>hydrophobic domain</scene> which is situated into the membrane. The human angiotensin receptor is therefore an ~~alpha~~ helical trans-membrane protein.

and <scene name='82/829348/B_sheet/1'>3 β sheets</scene>. Moreover, 7 α helix are made of a majority of hydrophobic amino acids. These helix are long enough to cross the membrane and create an <scene name='82/829348/Transmambrane_protein/1'>hydrophobic domain</scene> which is situated into the membrane. The human angiotensin receptor is therefore an α helical trans-membrane protein.

Since the angiotensin receptor belongs to the GPCRs family, those 7 ~~alpha~~ helix contain 3 extracellular and 3 intracellular loops.

Since the angiotensin receptor belongs to the GPCRs family, those 7 α helix contain 3 extracellular and 3 intracellular loops. The N terminus corresponds to the extracellular domain. The C terminal domain is located intracellularly.

The N terminus corresponds to the extracellular domain~~. The protein is made of three intracellular loops and three extracellular loops~~. The C terminal domain is located intracellularly.

=== Ligand binding pocket ===

In the extracellular environment, there is a β-hairpin in conjugation with <scene name='82/829348/Disulfuric_bridge/1'>two extracellular disulfure bridges</scene>. This structure is responsible for the opening and the locking of the ligand binding pocket <ref> PMID: 23386604 </ref>. The ligand goes into an <scene name='82/829348/Ligand_blinding_pocket/1'>hydrophilic pocket</scene> created into the membrane thanks to the 7 ~~alpha~~ helix which create a gate between the membrane and the extracellular environment.

In the extracellular environment, there is a β-hairpin in conjugation with <scene name='82/829348/Disulfuric_bridge/1'>two extracellular disulfure bridges</scene>. This structure is responsible for the opening and the locking of the ligand binding pocket <ref> PMID: 23386604 </ref>. The ligand goes into an <scene name='82/829348/Ligand_blinding_pocket/1'>hydrophilic pocket</scene> created into the membrane thanks to the 7 α helix which create a gate between the membrane and the extracellular environment.

AngII mediates AT1 receptor activation via stacking interactions between Phe8(AngII)/<scene name='82/829348/His_256/2'>His256</scene>(AT1 receptor) and Tyr4(AngII)/<scene name='82/829348/Asn_111/1'>Asn111</scene>(AT1 receptor). This phenomenon results in a conformational change in transmembrane (TM)3-TM6 helices and in interaction between TM2 and TM7.

~~=== G protein-binding site ===~~

When the angiotensin II binds to the angiotensin receptor in the ligand binding pocket, the conformation of the trans-membrane domain changes to create a cytosolic cleft for the binding and activation of G proteins. In this cleft, several conserved residues can be found, which form functional motifs present in all [[GPCRs]] <ref> PMID:30608150 </ref>.

=== Interaction with drugs ===

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Many ARBs contain a [https://en.wikipedia.org/wiki/Tetrazole tetrazole] group. Studies showed that tetrazole plays an important role in the binding with AT1R.

=== G protein-binding site ===

When the angiotensin II binds to the angiotensin receptor in the ligand binding pocket, the conformation of the trans-membrane domain changes to create a cytosolic cleft for the binding and activation of G proteins. In this cleft, several conserved residues can be found, which form functional motifs present in all [[GPCRs]] <ref> PMID:30608150 </ref>.

=== Interaction with other GPCRs ===

Sandbox Reserved 1095: Difference between revisions

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@@ Line 27: / Line 27: @@
 === Primary and secondary structure ===
 AT1 receptor consists in a 376 amino acid string <ref> [http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?pdbcode=4zud&template=main.html Protein Database (PDBsum): 4zud. European Bioinformatics (EBI); 2013.]</ref>. The protein is composed of
-<scene name='82/829348/Helix_a/1'>18 alpha helix</scene>
+<scene name='82/829348/Helix_a/1'>18 α helix</scene>
-and <scene name='82/829348/B_sheet/1'>3 β sheets</scene>. Moreover, 7 alpha helix are made of a majority of hydrophobic amino acids. These helix are long enough to cross the membrane and create an <scene name='82/829348/Transmambrane_protein/1'>hydrophobic domain</scene> which is situated into the membrane. The human angiotensin receptor is therefore an alpha helical trans-membrane protein.
+and <scene name='82/829348/B_sheet/1'>3 β sheets</scene>. Moreover, 7 α helix are made of a majority of hydrophobic amino acids. These helix are long enough to cross the membrane and create an <scene name='82/829348/Transmambrane_protein/1'>hydrophobic domain</scene> which is situated into the membrane. The human angiotensin receptor is therefore an α helical trans-membrane protein.
-Since the angiotensin receptor belongs to the GPCRs family, those 7 alpha helix contain 3 extracellular and 3 intracellular loops.
+Since the angiotensin receptor belongs to the GPCRs family, those 7 α helix contain 3 extracellular and 3 intracellular loops. The N terminus corresponds to the extracellular domain. The C terminal domain is located intracellularly.
-The N terminus corresponds to the extracellular domain. The protein is made of three intracellular loops and three extracellular loops. The C terminal domain is located intracellularly.
 === Ligand binding pocket ===
-In the extracellular environment, there is a β-hairpin in conjugation with <scene name='82/829348/Disulfuric_bridge/1'>two extracellular disulfure bridges</scene>. This structure is responsible for the opening and the locking of the ligand binding pocket <ref> PMID: 23386604  </ref>. The ligand goes into an <scene name='82/829348/Ligand_blinding_pocket/1'>hydrophilic pocket</scene> created into the membrane thanks to the 7 alpha helix which create a gate between the membrane and the extracellular environment.
+In the extracellular environment, there is a β-hairpin in conjugation with <scene name='82/829348/Disulfuric_bridge/1'>two extracellular disulfure bridges</scene>. This structure is responsible for the opening and the locking of the ligand binding pocket <ref> PMID: 23386604  </ref>. The ligand goes into an <scene name='82/829348/Ligand_blinding_pocket/1'>hydrophilic pocket</scene> created into the membrane thanks to the 7 α helix which create a gate between the membrane and the extracellular environment.
 AngII mediates AT1 receptor activation via stacking interactions between Phe8(AngII)/<scene name='82/829348/His_256/2'>His256</scene>(AT1 receptor) and Tyr4(AngII)/<scene name='82/829348/Asn_111/1'>Asn111</scene>(AT1 receptor). This phenomenon results in a conformational change in transmembrane (TM)3-TM6 helices and in interaction between TM2 and TM7.
-=== G protein-binding site ===
-When the angiotensin II binds to the angiotensin receptor in the ligand binding pocket, the conformation of the trans-membrane domain changes to create a cytosolic cleft for the binding and activation of G proteins. In this cleft, several conserved residues can be found, which form functional motifs present in all [[GPCRs]] <ref> PMID:30608150 </ref>.
 === Interaction with drugs ===
@@ Line 48: / Line 43: @@
 Many ARBs contain a [https://en.wikipedia.org/wiki/Tetrazole tetrazole] group. Studies showed that tetrazole plays an important role in the binding with AT1R.
+=== G protein-binding site ===
+When the angiotensin II binds to the angiotensin receptor in the ligand binding pocket, the conformation of the trans-membrane domain changes to create a cytosolic cleft for the binding and activation of G proteins. In this cleft, several conserved residues can be found, which form functional motifs present in all [[GPCRs]] <ref> PMID:30608150 </ref>.
 === Interaction with other GPCRs ===